INVESTIGATIONS ON STEROIDS. X. REVISION OF NOMENCLATURE OF PREVIOUSLY DESCRIBED COMPOUNDS¹

Abstract

In a number of publications from this laboratory (1,2,3,4,5) various 5,6oxides and 3,5,6-triols had been assigned arbitrary configurations at carbon atoms 5 and 6. Recent investigations performed in several laboratories, notably that of Ruzicka, now make it possible to define more accurately the configuration of these compounds. It appears that the necessary revisions are rather comprehensive.The school of Ruzicka (6) established the configuration of the so-called acholesteryl oxide and of 0-cholesteryl oxide. They should now be labelled 5,6 (a) -oxidocholestane-3 (/3) -ol and 5,6 f/3)-oxidocoprostane-3 (ß) -ol respectively, designations which clearly express the configurations at both carbon atoms 5 and 6. The preceding arbitrary nomenclature was thus shown to be correct. Hattori (7) and later Baxter and Spring (8) studied the fission reactions of the two cholesteryl oxides, using water, hydrochloric acid, and glacial acetic acid. Fission of the oxide rings can also be brought about by catalytic hydrogenation 19, 9a, 10).2 The opening of the oxide rings is known to be accompanied by a change of configuration at the carbon atom at which the bond with the oxygen atom is ruptured, as has been shown e.g. in the sugar series flit. cf. 12). Applied to a or 0-cholesteryI oxide such a rupture may lead in each case to two different 1 Aided by grants from Sharp and Dohme, Inc., Philadelphia and from the American Cancer Society on the recommendation of the Committee on Growth of the National Research Council.2 Ruzicka (11) also studied the catalytic hydrogenation of the -oxide and /3-oxide of dehydroisoandrosterone acetate [3(/3)-acetoxy-5,6(a)-oxidoandrostane-17-one and 3(/3)acetoxy-5,6(/3)-oxidoetiocholane-17-one respectively]. The results were analogous to those obtained with the acetates of -cholesteryl oxide and ß-cholesteryl oxide respectively (9, 9a).

Investigations on steroids. XX. 6β- and 6α-Acetoxy- and Hrdroxy-Derivatives of Progesterone and Androstenedione

“…As was reported from this laboratory earlier (6), dehydration of 6/3-acetoxyallopregnane-5-ol-3,20-dione (I) with dry hydrogen chloride in "alcohol-free chloroform" led to a crystalline product interpreted3 as 6/3-acetoxyprogesterone (II) (7). On repeating the experiment in "redistilled dried chloroform," an amorphous a, /3-unsaturated ketone of the same composition was obtained which resisted all attempts at crystallization.…”

“…176.5-177.5°). The latter compound had been obtained previously (10, 7), though its true configuration at carbon atom 6 had not been recognized. Saponification of VIII and IX furnished 6/3-hydroxy-A4-androstene-3,17-dione (X) (m.p.…”

“…147-148°) which ivas rearranged to the thermodynamically more stable 6a-acetoxyprogesterone (III) (amorphous). The previously described crystalline (6,7) and amorphous (8, 7) 6-acetoxyprogesterone represent the 6/3-and the 6«-epimers respectively. Saponification of II and III gave 6/3-hydroxyprogesterone (IV) (m.p.…”

“…1054, 1060). 7 According to findings of Drs. George W. Corner and S. Reynolds in 1942 which had remained unpublished.…”

“…Tests on higher dosage levels are under way. was originally (10) assigned the structure of 6a-acetoxy-A4-androstene-3,17dione (IX), but was later (7) interpreted to be 6/S-acetoxy-A4-androstene-3,17dione (VIII). Depending on the character of the solvent, one would expect the formation of two epimers.…”